Cheifetz S, Li I W, McCulloch C A, Sampath K, Sodek J
MRC Group in Periodontal Physiology, Faculty of Dentistry, University of Toronto, Ont., Canada.
Connect Tissue Res. 1996;35(1-4):71-8. doi: 10.3109/03008209609029176.
The bone morphogenetic proteins (BMPs) and transforming growth factor-beta s (TGF-beta s), are a group of structurally related proteins which have been shown to stimulate bone formation in vivo. Since these proteins are concentrated in the organic matrix of bone and would be released during bone resorption, they are likely to have a profound effect on the remodeling bone and may provide a link between bone resorption and bone formation. We are using primary cultures of fetal rat calvarial cells (FRCC) to study the independent and combined effects of OP-1/BMP-7 and TGF-beta 1 on bone cells at different stages of differentiation in order to identify responding cell populations and target genes. We have confirmed prior reports that OP-1 stimulates, while TGF-beta 1 inhibits, osteogenic differentiation in this system. The increase in both number and size of the mineralized nodules induced by OP-1 was accompanied by increased expression of alkaline phosphatase and type I collagen with an induction of bone sialoprotein (BSP) suggesting that OP-1 stimulates both differentiation and clonal expansion of osteoblastic cells. Interestingly, TGF-beta 1 abrogated OP-1 induced nodule formation. Despite these opposing effects on osteogenic differentiation, TGF-beta 1 (Wrana et al, 1991) and OP-1 both stimulated a rapid induction of osteopontin (OPN) mRNA in confluent FRCC cultures enriched in pre-osteoblastic cells. In contrast, when OP-1 was added to nodule-forming cultures which are enriched in osteoblastic cells, there was only a weak induction of OPN. Moreover, while the expression of one marker for mature osteoblasts (BSP) was refractory to OP-1, another (osteocalcin) was markedly stimulated. Thus OP-1 has selective effects on bone matrix protein expression that are dependent on the differentiated state of the cells.
骨形态发生蛋白（BMPs）和转化生长因子-β（TGF-βs）是一组结构相关的蛋白质，已被证明在体内可刺激骨形成。由于这些蛋白质集中在骨的有机基质中，并会在骨吸收过程中释放，它们可能对重塑骨有深远影响，并可能在骨吸收和骨形成之间提供联系。我们正在使用胎鼠颅骨细胞（FRCC）的原代培养物来研究OP-1/BMP-7和TGF-β1对不同分化阶段骨细胞的独立作用和联合作用，以确定反应细胞群体和靶基因。我们已经证实了先前的报道，即OP-1在该系统中刺激成骨分化，而TGF-β1则抑制成骨分化。OP-1诱导的矿化结节数量和大小的增加伴随着碱性磷酸酶和I型胶原蛋白表达的增加，并诱导骨唾液蛋白（BSP）表达，这表明OP-1刺激成骨细胞的分化和克隆扩增。有趣的是，TGF-β1消除了OP-1诱导的结节形成。尽管对成骨分化有这些相反的作用，但TGF-β1（Wrana等人，1991年）和OP-1都在富含前成骨细胞的汇合FRCC培养物中刺激了骨桥蛋白（OPN）mRNA的快速诱导。相反，当将OP-1添加到富含成骨细胞的结节形成培养物中时，OPN的诱导作用较弱。此外，虽然一种成熟成骨细胞标记物（BSP）的表达对OP-1不敏感，但另一种（骨钙素）则受到明显刺激。因此，OP-1对骨基质蛋白表达具有选择性作用，这取决于细胞的分化状态。
